Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus.

Abstract

BACKGROUND:

Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART).

METHODS:

We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350-500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject's age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses.

RESULTS:

Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37-.86), AIDS-defining cancers (HR 0.23; 95% CI, .11-.49), any virus-related cancer (HR 0.30; 95% CI, .16-.54), Kaposi sarcoma (HR 0.25; 95% CI, .10-.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06-.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference -1.6; 95% CI, -2.8, -.5).

CONCLUSIONS:

Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.

• Authors: Michael J Silverberg, Wendy Leyden, Raúl U Hernández-Ramírez, Li Qin, Haiqun Lin, Amy C Justice, Nancy A Hessol, Chad J Achenbach, Gypsyamber D'Souza, Eric A Engels, Keri N Althoff, Angel M Mayor, Timothy R Sterling, Mari M Kitahata, Ronald J Bosch, Michael S Saag, Charles S Rabkin, Michael A Horberg, M John Gill, Surbhi Grover, W Christopher Mathews, Jun Li, Heidi M Crane, Stephen J Gange, Bryan Lau, Richard D Moore, Robert Dubrow, Romain S Neugebauer
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 72 Issue 11 Pg. 1900-1909 (06 01 2021) ISSN: 1537-6591 [Electronic] United States
• PMID: 32785640 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Topics

• Acquired Immunodeficiency Syndrome
• CD4 Lymphocyte Count
• HIV
• HIV Infections (complications, drug therapy, epidemiology)
• Humans
• Neoplasms (epidemiology)
• Sarcoma, Kaposi